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Hypoxia enhances buffalo adipose-derived mesenchymal stem cells proliferation,stemness, and reprogramming into induced pluripotent stem cells |
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| Authors: | Yanfei Deng Guiting Huang Feng Chen Eric David Testroet Hui Li Haiyang Li Tianying Nong Xiaoling Yang Jiayu Cui Deshun Shi Sufang Yang |
| Affiliation: | 1. Animal Reproduction Institute, State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi University, Nanning, China;2. Animal Reproduction Institute, State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi University, Nanning, China Reproductive Medicine Center, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China Deng and Huang have contributed equally to this study.;3. Department of Animal and Veterinary Sciences, University of Vermont, Burlington, Vermont |
| Abstract: | Adipose tissue-derived mesenchymal stem cells (ASCs) from livestock are valuable resources for animal reproduction and veterinary therapeutics. Previous studies have shown that hypoxic conditions were beneficial in maintaining the physiological activities of ASCs. However, the effects of hypoxia on buffalo ASCs (bASCs) remain unclear. In this study, the effects of hypoxia on proliferation, stemness, and reprogramming into induced pluripotent stem cells (iPSCs) of bASCs were examined. The results showed that the hypoxic culture conditions (5% oxygen) enhanced the proliferation and colony formation of bASCs. The expression levels of proliferation-related genes, and secretion of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were significantly enhanced in hypoxia. Hypoxic culture conditions activated hypoxia-inducible factor-1α (HIF-1α), thereby contributing to the secretion of bFGF and VEGF, which in turn enhanced the expression of HIF-1α and promoted the proliferation of bASCs. Furthermore, in hypoxic culture conditions, bASCs exhibited the main characteristics of mesenchymal stem cells, and the expression levels of the pluripotent markers OCT4, NANOG, C-MYC, and the differentiation capacity of bASCs were significantly enhanced. Finally, bASCs were more efficiently and easily reprogrammed into iPSCs in hypoxic culture conditions and these iPSCs exhibited some characteristics of naïve pluripotent stem cells. These findings provide the theoretical guidance for elucidating the detailed mechanism of hypoxia on physiological activities of bASCs including proliferation, stemness maintenance, and reprogramming. |
| Keywords: | buffalo adipose-derived mesenchymal stem cells hypoxia pluripotency proliferation reprogramming |